This proposal requests support for an ongoing research training program centered in the Hematology Section of the Department of Internal Medicine at Yale University School of Medicine. The Program provides trainees with the research experience needed to develop independent careers in areas relevant to blood diseases. Its primary objective will continue to be development of the investigative careers of M.D., Ph.D., and M.D./Ph.D. trainees. Two to three fellows per year will be recruited for intensive laboratory-based research training lasting 2-3 years. A typical M.D. or M.D./Ph.D. trainee will have already completed residency and one year of clinical training in hematology/oncology. Ph.D. postdoctoral trainees with research interests in molecular and cellular hematology/oncology are also recruited to the program. Trainees devote 80-90% effort to bench research supervised by a participating faculty member. Research experience is supplemented by participation in Sectional, Departmental, and campus-wide seminars, national meetings, and graduate level courses, including courses on research methods and the responsible conduct of research. Research progress and career development is monitored by a progress committee consisting of the research mentor, program director, and two participating faculty members. Research opportunities emphasize cellular and molecular biological analysis of tissues and molecules important for differentiation, function, and diseases of blood cells, including: erythrocyte membrane skeleton protein genes, and their genetic disorders;hematopoietic stem cell biology;genomics and proteomics;lymphoid and monocytic surface molecules;early events in hematopoietic cell differentiation;granulocyte maturation;oncogene expression;immunohematology;molecular virology;immunogenetics;gene transfer;molecular oncology;and endothelial cell biology. Research training takes place within the outstanding research environment of Yale University in well equipped and funded laboratories. The participating faculty includes academic hematologists and oncologists, and basic scientists in the fields of genetics, molecular biology, pathology, cell biology, immunobiology, and basic biology, many of whom are nationally and internationally renowned, and are united by common research interests and collaborations. The program offers trainees an opportunity to perform meaningful research and to develop investigative careers in hematology within a fertile intellectual environment populated by an outstanding interdisciplinary faculty.